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Vasodilator effects of nitric oxide donor [Ru (terpy) (bdq) NO +] 3+ in cava vein and basilar artery of normotensive and renal hypertensive rat (2K-1C).

Grant number: 08/03075-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2008
Effective date (End): May 31, 2011
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Lusiane Maria Bendhack
Grantee:Michele Paulo Schiavi
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The study of Furchgott and Zawadsky (1980) , has established the importance of the endothelium to the control of vascular tone. This study found that the derived relaxing factor of the endothelium was nitric oxide (NO). The NO is the main agent endogenous vasodilator that regulates the vascular tonus, homeostasis and blood flow. Studies report that the reduction in the synthesis and the bioavailability of NO can lead to cardiovascular diseases. Thus, there is a great interest in chemical compounds that can serve as a vehicle for the NO release in biological systems. However, NO donors, including the most used in the clinic, nitroglycerin (NTG) and sodium nitroprusside (SNP), have important limitations to their use which confronted with its benefits as development of tolerance and side effects due the release of toxic products. Thus, there is a great interest in the development of new chemical compounds that could serve as a vehicle for the NO release in biological systems. Among the compounds widely studied, which are capable of releasing NO in organisms, are complex nitrosilos of ruthenium. Our research group has studied several of these complexes which have different chemical and biological characteristics. These studies demonstrate the vasodilator action of compounds that release NO by chemical reduction and compounds that release NO by light irradiation. Our main interest in the study of these macrociclics compounds act as NO donors is a potential anti-hypertensive drug. The hypertension is characterized, among other factors, by increased peripheral vascular resistance with a consequent increase in blood pressure. Various models of hypertension are used experimentally to study the mechanisms involved in this process. Among them, the model of renal hypertension 2 Kidney-1 Clip (2K-1C). The hypothesis of this study is that the compound NO donor [Ru (terpy) (bdq) NO +] 3 + is able to reduce blood pressure by acting on smooth muscle cells. The hypotensive effects could be due to vasodilation of veins and / or arteries of resistance, isolated from normotensive and hypertensive rats. The compost NO donor [Ru (terpy) (bdq) NO +] 3 +, which will be used in our study, has accelerated its release of NO in the presence of light. It has been verified by our group that this compound induces vascular relaxation, involving NO and hydroxyl ions (NO-) in the aorta rings of rats (BONAVENTURA et al., 2007) and has less effect vasodilator in the aorta isolated from 2K - 1C than normotensive rats (Rodrigues et al., 2008).

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